Radon in homes and risk of lung cancer: collaborative analysis of indi
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《英国医生杂志》
1 Clinical Trials Service Unit and Epidemiological Studies Unit, Radcliffe Infirmary, Oxford OX2 6HE, 2 School of Public Health, University of Tampere, Tampere, Finland, 3 Area of Preventive Medicine and Public Health, University of Santiago de Compostela, Spain, 4 Institut de Radioprotection et de S?reté Nucléaire, Direction de la Radioprotection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Fontenay-aux-Roses Cedex, France, 5 Unit of Radioactivity and its Health Effects, Department of Technology and Health, Italian National Institute of Health, Rome, Italy, 6 Department of Applied Statistics, University of Reading, Reading RG6 2AL, 7 Swedish Radiation Protection Authority, SE-171 16, Stockholm, Sweden, 8 Department of Epidemiology, Rome E Health Authority, Rome, Italy, 9 Finnish Cancer Registry, Helsinki, Finland, 10 Institute of Epidemiology, GSF Research Centre for Environment and Health, Neuherberg, Germany, 11 Institute of Biometry, Epidemiology and Information Processing, University of Veterinary Medicine, Hannover, Germany, 12 Department of Radiation Protection and Health, Federal Office for Radiation Protection, Neuherberg, Germany, 13 Institute of Environmental Medicine, Karolinska Institute, S-171 77, Stockholm, Sweden, 14 STUK-Radiation and Nuclear Safety Authority, Helsinki, Finland, 15 National Radiological Protection Board, Chilton, Didcot OX11 0RQ, 16 Tumorregister Tirol, Innsbruck, Austria, 17 Epidemiology Unit, National Radiation Protection Institute, Prague, Czech Republic, 18 Department of Social Medicine, University of Bristol, Bristol BS8 2PR
Correspondence to: S Darby sarah.darby@ctsu.ox.ac.uk
Abstract
In many countries exposure in the home to short lived radioactive disintegration products of the chemically inert gas radon-222 is responsible for about half of all non-medical exposure to ionising radiation.1 Radon-222 arises naturally from the decay of uranium-238, which is present throughout the earth's crust. It has a half life of four days, allowing it to diffuse through soil and into the air before decaying by emission of an particle into a series of short lived radioactive progeny. Two of these, polonium-218 and polonium-214, also decay by emitting particles. If inhaled, radon itself is mostly exhaled immediately. Its short lived progeny, however, which are solid, tend to be deposited on the bronchial epithelium, thus exposing cells to irradiation.
Air pollution by radon is ubiquitous. Concentrations are low outdoors but can build up indoors, especially in homes, where most exposure of the general population occurs. The highest concentrations to which workers have been routinely exposed occur underground, particularly in uranium mines. Studies of exposed miners have consistently found associations between radon and lung cancer.2 3 Extrapolation from these studies suggests that in many countries residential radon, which involves lower exposure in much larger numbers of people, could cause a substantial minority of all lung cancers. This is of practical relevance because radon concentrations in existing buildings can usually be reduced at moderate cost—for example, by increasing underfloor ventilation—while low concentrations can usually be ensured at reasonable or low cost in new buildings—for example, by installing a radon proof barrier at ground level. These extrapolations, however, depend on uncertain assumptions because the levels of exposure in miners that produced evident risk were usually much higher, lasted only a few years, and took place under different particulate air and other conditions.1-3 Moreover, history on smoking is often lacking, or limited, in the studies of miners and some miners were also exposed to other lung carcinogens such as arsenic.
Studies to estimate directly the risk of lung cancer associated with residential radon exposure over several decades have been conducted in many European countries. Individually these studies have not been large enough to assess moderate risks reliably. Greater statistical power can be achieved by combining information from several studies, but this cannot be done satisfactorily from published information. Urban areas tend to have lower radon concentrations than rural ones as the underlying rock is usually sedimentary and more people live upstairs in apartments. Urban areas also usually have a higher prevalence of smoking. Hence, radon concentrations in homes tend to be negatively correlated with smoking,4-6 and a large dataset is needed to correct for this reliably. We therefore brought together and reanalysed individual data from all European studies of residential radon and lung cancer that satisfied certain criteria.
Methods
Our analysis included 7148 people with lung cancer and 14 208 controls. For cases of lung cancer the mean measured radon concentration was 104 Bq/m3 while for controls the weighted average of the study specific means, with weights proportional to numbers of cases of lung cancer, was 97 Bq/m3 (table 1). Among controls, the percentage who were lifelong non-smokers increased as radon concentration increased (percentages were 39%, 40%, 41%, 46%, and 48% for measured radon < 100, 100-199, 200-399, 400-799, and 3 800 Bq/m3 after stratification for study, age, sex, and region of residence; P = 0.001 for trend).
Table 1 European case-control studies of residential radon and lung cancer
Risk of lung cancer versus measured radon concentration
After we stratified for study, age, sex, region of residence, and smoking the risk of lung cancer increased by 8.4% (95% confidence interval 3.0% to 15.8%; P = 0.0007) per 100 Bq/m3 increase in measured radon concentration. We stratified for smoking by first subdividing the individuals into seven categories (lifelong non-smokers, current smokers of < 15, 15-24, or 25 cigarettes a day, ex-smokers for < 10 years or 10 years, and others) and then further subdividing each group of current smokers by the age at which they started smoking (< 15, 15-17, 18-20, or 21 years or unknown) and each group of ex-smokers by amount previously smoked (< 15, 15-24, or 25 a day or unknown). If smoking had been omitted from the stratification, the risk of lung cancer would have increased by only 2.3% per 100 Bq/m3 increase in measured radon, and if it had been included with only seven categories, the estimated increase would have been 5.2%. In all subsequent analyses we used the full smoking stratification.
The proportionate increase in risk was not strongly influenced by any one study. When we re-estimated the risk omitting each study in turn, it changed at most by a fifth. Nor did it vary substantially according to the period used to calculate radon exposures. The above analyses relate to measured radon concentrations 5-34 years earlier. Measured radon in periods 5-14, 15-24, and 25-34 years earlier were highly correlated, so the relation of risk to radon in each of these three periods was similar to that for the entire period (7.5%, 7.6%, and 6.6%, respectively). When we considered radon concentrations throughout the period 5-34 years earlier but with contributions from periods 5-14, 15-24, and 25-34 years earlier weighted in proportions 1.0:0.75:0.50, as suggested by the miners' studies,2 the risk was unaltered, at 8.4% per 100 Bq/m3 of measured radon.
When we subdivided study participants according to seven categories of measured radon (table 2), the results were consistent with a linear dose-response relation (fig 1). There was no significant curvature of the best fitting regression line, and no point differed significantly from this line. The linear relation remained significant even when we limited analysis to measured concentrations < 200 Bq/m3 (P = 0.04). When we compared individuals with measured radon 100-199 Bq/m3 (mean 136 Bq/m3) versus those with measured radon < 100 Bq/m3 (mean 52 Bq/m3) the relative risk was 1.20 (95% confidence interval 1.03 to 1.30; P = 0.01). Models with no effect up to a "threshold" dose and then a linear effect did not fit significantly better than a linear effect with no threshold; in such models the upper 95% confidence limit for a possible threshold was 150 Bq/m3 measured radon.
Table 2 Relative risk of lung cancer by radon concentration (Bq/m3) in homes 5-34 years previously
Fig 1 Relative risk of lung cancer according to measured residential radon concentration and usual residential radon concentration, with best fitting straight lines (risks are relative to that at 0 Bq/m3)
Effect modification
There was no good evidence that the proportionate increase in lung cancer risk per 100 Bq/m3 measured radon differed by study (P = 0.94), age (P = 0.93), sex (P = 0.19), or smoking status (P = 0.98) (fig 2). We rejected a model in which the combined effects of radon and smoking were additive (P = 0.05). When we considered lifelong non-smokers separately the increase in risk per 100 Bq/m3 was 10.6% (0.3% to 28.0%), and there was no evidence that it varied according to age, sex, or smoking status of the individual's spouse (P = 0.46, 0.19, and 0.18, respectively).
Fig 2 Percentage increase in risk of lung cancer per 100 Bq/m3 increase in measured radon concentration by study, age, sex, smoking, and histological type. Squares have areas inversely proportional to the square of the standard error of the percentage increase. For the Spanish study, the present non-significantly negative estimate differs from a previously published positive estimate based on quartiles of radon distribution.16 The negative estimate, based on individual radon concentrations, is dominated by three cases and 17 controls with measured radon 400 Bq/m3
Microscopic confirmation of the diagnosis of lung cancer was available for 6310 individuals. The variation between the dose-response relations for the four histological types, as classified by the original studies, did not reach significance (P = 0.07, fig 2). The increase in risk per 100 Bq/m3 measured radon, however, was 31.2% (12.8% to 60.6%) for small cell lung cancer, while for all other histological types combined it was 2.6% (< 0% to 10.2%) (P = 0.03 for difference), in accordance with the steeper dose-response relation reported for small cell cancer in early studies of miners exposed to radon.2
Allowance for random uncertainties in estimates of radon exposure
Measurements of radon concentrations in individuals' homes during the period 5-34 years previously are subject to substantial uncertainty. This uncertainty is not symmetrical. For example, if the true average long term concentration that an individual was exposed to was actually 300 Bq/m3, then the measured value for that individual could, by chance, be 500 too high (that is, 800 Bq/m3), especially if it depended on measurements in only one or two homes, but it could not be 500 too low. Detailed investigation of all available data concerning the variability in radon concentrations when the same house was measured in two different years suggests that, for most individuals with measured levels above 800 Bq/m3, the measured value was substantially higher than the usual or true long term average value.7 Hence, although in the group with measured radon concentrations above 800 Bq/m3 the mean of the measured concentrations was 1204 Bq/m3, the estimated mean of their usual radon concentrations was only 678 Bq/m3 (table 2). If the mean usual radon concentration in this highly exposed group is only about half the mean measured value, then the slope of the line of risk versus usual radon concentration becomes about twice as steep as that of the line of risk versus measured radon concentration. When we re-estimated the risk of lung cancer, correcting for random uncertainties in measuring radon concentrations, it increased to 16% (5% to 31%) per 100 Bq/m3 usual radon. The dose-response relation with usual radon was consistent with a linear model (fig 1). Again there was no evidence that the risk per 100 Bq/m3 differed according to age, sex, or smoking.7
Combined effect of smoking and radon on absolute risk of lung cancer
For current smokers of 15-24 cigarettes a day the risk of lung cancer relative to that in lifelong non-smokers was 25.8 (21.3 to 31.2) for men in all 13 studies combined (after stratification by study, age, and region). Therefore, similarity of the relative risk between smokers and lifelong non-smokers would imply substantial differences in absolute risk per 100 Bq/m3. If the risk of lung cancer increases by about 16% per 100 Bq/m3 usual radon, regardless of smoking status, then at usual radon levels of 0, 100, 400, and 800 Bq/m3, respectively, cumulative absolute risks of lung cancer by age 75 years would be 0.41%, 0.47%, 0.67%, and 0.93% in lifelong non-smokers and 10.1%, 11.6%, 16.0%, and 21.6% in cigarette smokers (fig 3).
Fig 3 Cumulative absolute risk of death from lung cancer by age 75 years versus usual radon concentration at home for cigarette smokers and lifelong non-smokers. Plotted values calculated using relative risks for smoking from men in all studies combined, and absolute risks in lifelong non-smokers from US data for men and women combined.20 Areas of circles proportional to numbers of controls with usual radon levels in ranges <200, 200-399, 400-599, and 600 Bq/m3
Discussion
United Nations Scientific Committee on the Effects of Atomic Radiation. Sources and Effects of Ionizing Radiation. UNSCEAR 2000 Report to the General Assembly, with Scientific Annexes. Vol I: Sources. New York: United Nations, 2000.
National Research Council. Committee on health risks of exposure to radon (BEIR VI). Health effects of exposure to radon. Washington, DC: National Academy Press, 1999.
International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans. Vol 78. Ionizing radiation. Part 2: Some internally deposited radionuclides. Lyons: IARC, 2001.
Puskin JS. Smoking as a confounder in ecologic correlations of cancer mortality rates with average county radon levels. Health Physics 2003;84: 526-32.
Heid IM, Schaffrath Rosario A, Kreienbrock L, Küchenhoff H, Wichmann HE. The impact of measurement error on studies on lung cancer and residential radon exposure in Germany. J Toxicol Environ Health (in press).
Darby S, Whitley E, Silcocks P, Thakrar B, Green M, Lomas P, et al. Risk of lung cancer associated with residential radon exposure in south-west England: a case-control study. Br J Cancer 1998;78: 394-408.
Darby S, Hill D, Deo H, Auvinen A, Barros-Dios JM, Baysson H, et al. Residential radon and lung cancer: detailed results of a collaborative analysis of individual data on 7,148 subjects with lung cancer and 14, 208 subjects without lung cancer from 13 epidemiological studies in Europe. Scand J Work Environ Health (in press).
Lagarde F, Pershagen G, ?kerblom G, Axelson O, B?verstam U, Damber L, et al. Residential radon and lung cancer in Sweden: risk analysis accounting for random error in the exposure assessment. Health Phys 1997;72: 269-76.
Oberaigner W, Kreienbrock L, Schaffrath Rosario A, Kreuzer M, Wellmann J, Lerrer G, et al. Radon und Lungenkrebs im Bezirk Imst/?sterreich. Fortschritte in der Umweltmedizin. Landsberg am Lech: Ecomed Verlagsgesellschaft, 2002.
Tomáek L, Müller T, Kunz E, Heribanová A, Matzner J, Plaèek V, et al. Study of lung cancer and residential radon in the Czech Republic. Cent Eur J Public Health 2001;9: 150-3.
Auvinen A, M?kel?inen I, Hakama M, Castrén O, Pukkala E, Reisbacka H, et al. Indoor radon exposure and risk of lung cancer: a nested case-control study in Finland. J Natl Cancer Inst 1996;88: 966-72 (plus erratum 1998;90:401-02).
Ruosteenoja E, M?kel?inen I, Ryt?maa T, Hakulinen T, Hakama M. Radon and lung cancer in Finland. Health Phys 1996;71: 185-9.
Baysson H, Tirmarche M, Tymen G, Gouva S, Caillaud D, Artus JC, et al. Case-control study on lung cancer and indoor radon in France. Epidemiology 2004;15: 709-16.
Wichmann HE, Shaffrath Rosario A, Heid IM, Kreuzer M, Heinrich J, Kreienbrock L. Lung cancer risk due to residential radon in a pooled and extended analysis of studies in Germany. Health Physics (in press).
Bochicchio F, Forastiere F, Farchi S, Quarto M, Axelson A. Residential radon exposure, diet and lung cancer: a case-control study in a Mediterranean region. Int J Cancer (in press).
Barros-Dios JM, Barreiro MA, Ruano-Ravina A, Figueiras A. Exposure to residential radon and lung cancer in Spain: a population-based case-control study. Am J Epidemiol 2002;156: 548-55.
Pershagen G, ?kerblom G, Axelson O, Clavensj? B, Damber L, Desai G, et al. Residential radon exposure and lung cancer in Sweden. N Engl J Med 1994;330: 159-64.
Lagarde F, Axelsson G, Damber L, Mellander H, Nyberg F, Pershagen G. Residential radon and lung cancer among never-smokers in Sweden. Epidemiology 2001;12: 396-404.
Pershagen G, Liang Z-H, Hrubec Z, Svensson C, Boice Jr JD. Residential radon exposure and lung cancer in Swedish women. Health Phys 1992;63: 179-86.
Peto R, Lopez A, Boreham J, Thun M, Heath C. Mortality from tobacco in developed countries: indirect estimation from national vital statistics. Lancet 1992;339: 1268-78.
Krewski D, Lubin JH, Zielinski JM, Alavanja M, Catalan VS, Field RW, et al. A combined analysis of North American case-control studies of residential radon and lung cancer. Epidemiology (in press).
Lubin JH, Wang ZY, Boice JD Jr, Xu ZY, Blot WJ, Wang LD, et al. Risk of lung cancer and residential radon in China: pooled results of two studies. Int J Cancer 2004;109: 132-7.
Pavia M, Bianco A, Pileggi C, Angelillo IF. Meta-analysis of residential exposure to radon gas and lung cancer. Bull World Health Organ 2003;81: 732-8.
Lubin JH, Tomáek L, Edling C, Hornung RW, Howe G, Kunz E, et al. Estimating lung cancer mortality from residential radon using data for low exposures of miners. Radiat Res 1997;147: 126-34.
((S Darby, professor of medical statistics)
Correspondence to: S Darby sarah.darby@ctsu.ox.ac.uk
Abstract
In many countries exposure in the home to short lived radioactive disintegration products of the chemically inert gas radon-222 is responsible for about half of all non-medical exposure to ionising radiation.1 Radon-222 arises naturally from the decay of uranium-238, which is present throughout the earth's crust. It has a half life of four days, allowing it to diffuse through soil and into the air before decaying by emission of an particle into a series of short lived radioactive progeny. Two of these, polonium-218 and polonium-214, also decay by emitting particles. If inhaled, radon itself is mostly exhaled immediately. Its short lived progeny, however, which are solid, tend to be deposited on the bronchial epithelium, thus exposing cells to irradiation.
Air pollution by radon is ubiquitous. Concentrations are low outdoors but can build up indoors, especially in homes, where most exposure of the general population occurs. The highest concentrations to which workers have been routinely exposed occur underground, particularly in uranium mines. Studies of exposed miners have consistently found associations between radon and lung cancer.2 3 Extrapolation from these studies suggests that in many countries residential radon, which involves lower exposure in much larger numbers of people, could cause a substantial minority of all lung cancers. This is of practical relevance because radon concentrations in existing buildings can usually be reduced at moderate cost—for example, by increasing underfloor ventilation—while low concentrations can usually be ensured at reasonable or low cost in new buildings—for example, by installing a radon proof barrier at ground level. These extrapolations, however, depend on uncertain assumptions because the levels of exposure in miners that produced evident risk were usually much higher, lasted only a few years, and took place under different particulate air and other conditions.1-3 Moreover, history on smoking is often lacking, or limited, in the studies of miners and some miners were also exposed to other lung carcinogens such as arsenic.
Studies to estimate directly the risk of lung cancer associated with residential radon exposure over several decades have been conducted in many European countries. Individually these studies have not been large enough to assess moderate risks reliably. Greater statistical power can be achieved by combining information from several studies, but this cannot be done satisfactorily from published information. Urban areas tend to have lower radon concentrations than rural ones as the underlying rock is usually sedimentary and more people live upstairs in apartments. Urban areas also usually have a higher prevalence of smoking. Hence, radon concentrations in homes tend to be negatively correlated with smoking,4-6 and a large dataset is needed to correct for this reliably. We therefore brought together and reanalysed individual data from all European studies of residential radon and lung cancer that satisfied certain criteria.
Methods
Our analysis included 7148 people with lung cancer and 14 208 controls. For cases of lung cancer the mean measured radon concentration was 104 Bq/m3 while for controls the weighted average of the study specific means, with weights proportional to numbers of cases of lung cancer, was 97 Bq/m3 (table 1). Among controls, the percentage who were lifelong non-smokers increased as radon concentration increased (percentages were 39%, 40%, 41%, 46%, and 48% for measured radon < 100, 100-199, 200-399, 400-799, and 3 800 Bq/m3 after stratification for study, age, sex, and region of residence; P = 0.001 for trend).
Table 1 European case-control studies of residential radon and lung cancer
Risk of lung cancer versus measured radon concentration
After we stratified for study, age, sex, region of residence, and smoking the risk of lung cancer increased by 8.4% (95% confidence interval 3.0% to 15.8%; P = 0.0007) per 100 Bq/m3 increase in measured radon concentration. We stratified for smoking by first subdividing the individuals into seven categories (lifelong non-smokers, current smokers of < 15, 15-24, or 25 cigarettes a day, ex-smokers for < 10 years or 10 years, and others) and then further subdividing each group of current smokers by the age at which they started smoking (< 15, 15-17, 18-20, or 21 years or unknown) and each group of ex-smokers by amount previously smoked (< 15, 15-24, or 25 a day or unknown). If smoking had been omitted from the stratification, the risk of lung cancer would have increased by only 2.3% per 100 Bq/m3 increase in measured radon, and if it had been included with only seven categories, the estimated increase would have been 5.2%. In all subsequent analyses we used the full smoking stratification.
The proportionate increase in risk was not strongly influenced by any one study. When we re-estimated the risk omitting each study in turn, it changed at most by a fifth. Nor did it vary substantially according to the period used to calculate radon exposures. The above analyses relate to measured radon concentrations 5-34 years earlier. Measured radon in periods 5-14, 15-24, and 25-34 years earlier were highly correlated, so the relation of risk to radon in each of these three periods was similar to that for the entire period (7.5%, 7.6%, and 6.6%, respectively). When we considered radon concentrations throughout the period 5-34 years earlier but with contributions from periods 5-14, 15-24, and 25-34 years earlier weighted in proportions 1.0:0.75:0.50, as suggested by the miners' studies,2 the risk was unaltered, at 8.4% per 100 Bq/m3 of measured radon.
When we subdivided study participants according to seven categories of measured radon (table 2), the results were consistent with a linear dose-response relation (fig 1). There was no significant curvature of the best fitting regression line, and no point differed significantly from this line. The linear relation remained significant even when we limited analysis to measured concentrations < 200 Bq/m3 (P = 0.04). When we compared individuals with measured radon 100-199 Bq/m3 (mean 136 Bq/m3) versus those with measured radon < 100 Bq/m3 (mean 52 Bq/m3) the relative risk was 1.20 (95% confidence interval 1.03 to 1.30; P = 0.01). Models with no effect up to a "threshold" dose and then a linear effect did not fit significantly better than a linear effect with no threshold; in such models the upper 95% confidence limit for a possible threshold was 150 Bq/m3 measured radon.
Table 2 Relative risk of lung cancer by radon concentration (Bq/m3) in homes 5-34 years previously
Fig 1 Relative risk of lung cancer according to measured residential radon concentration and usual residential radon concentration, with best fitting straight lines (risks are relative to that at 0 Bq/m3)
Effect modification
There was no good evidence that the proportionate increase in lung cancer risk per 100 Bq/m3 measured radon differed by study (P = 0.94), age (P = 0.93), sex (P = 0.19), or smoking status (P = 0.98) (fig 2). We rejected a model in which the combined effects of radon and smoking were additive (P = 0.05). When we considered lifelong non-smokers separately the increase in risk per 100 Bq/m3 was 10.6% (0.3% to 28.0%), and there was no evidence that it varied according to age, sex, or smoking status of the individual's spouse (P = 0.46, 0.19, and 0.18, respectively).
Fig 2 Percentage increase in risk of lung cancer per 100 Bq/m3 increase in measured radon concentration by study, age, sex, smoking, and histological type. Squares have areas inversely proportional to the square of the standard error of the percentage increase. For the Spanish study, the present non-significantly negative estimate differs from a previously published positive estimate based on quartiles of radon distribution.16 The negative estimate, based on individual radon concentrations, is dominated by three cases and 17 controls with measured radon 400 Bq/m3
Microscopic confirmation of the diagnosis of lung cancer was available for 6310 individuals. The variation between the dose-response relations for the four histological types, as classified by the original studies, did not reach significance (P = 0.07, fig 2). The increase in risk per 100 Bq/m3 measured radon, however, was 31.2% (12.8% to 60.6%) for small cell lung cancer, while for all other histological types combined it was 2.6% (< 0% to 10.2%) (P = 0.03 for difference), in accordance with the steeper dose-response relation reported for small cell cancer in early studies of miners exposed to radon.2
Allowance for random uncertainties in estimates of radon exposure
Measurements of radon concentrations in individuals' homes during the period 5-34 years previously are subject to substantial uncertainty. This uncertainty is not symmetrical. For example, if the true average long term concentration that an individual was exposed to was actually 300 Bq/m3, then the measured value for that individual could, by chance, be 500 too high (that is, 800 Bq/m3), especially if it depended on measurements in only one or two homes, but it could not be 500 too low. Detailed investigation of all available data concerning the variability in radon concentrations when the same house was measured in two different years suggests that, for most individuals with measured levels above 800 Bq/m3, the measured value was substantially higher than the usual or true long term average value.7 Hence, although in the group with measured radon concentrations above 800 Bq/m3 the mean of the measured concentrations was 1204 Bq/m3, the estimated mean of their usual radon concentrations was only 678 Bq/m3 (table 2). If the mean usual radon concentration in this highly exposed group is only about half the mean measured value, then the slope of the line of risk versus usual radon concentration becomes about twice as steep as that of the line of risk versus measured radon concentration. When we re-estimated the risk of lung cancer, correcting for random uncertainties in measuring radon concentrations, it increased to 16% (5% to 31%) per 100 Bq/m3 usual radon. The dose-response relation with usual radon was consistent with a linear model (fig 1). Again there was no evidence that the risk per 100 Bq/m3 differed according to age, sex, or smoking.7
Combined effect of smoking and radon on absolute risk of lung cancer
For current smokers of 15-24 cigarettes a day the risk of lung cancer relative to that in lifelong non-smokers was 25.8 (21.3 to 31.2) for men in all 13 studies combined (after stratification by study, age, and region). Therefore, similarity of the relative risk between smokers and lifelong non-smokers would imply substantial differences in absolute risk per 100 Bq/m3. If the risk of lung cancer increases by about 16% per 100 Bq/m3 usual radon, regardless of smoking status, then at usual radon levels of 0, 100, 400, and 800 Bq/m3, respectively, cumulative absolute risks of lung cancer by age 75 years would be 0.41%, 0.47%, 0.67%, and 0.93% in lifelong non-smokers and 10.1%, 11.6%, 16.0%, and 21.6% in cigarette smokers (fig 3).
Fig 3 Cumulative absolute risk of death from lung cancer by age 75 years versus usual radon concentration at home for cigarette smokers and lifelong non-smokers. Plotted values calculated using relative risks for smoking from men in all studies combined, and absolute risks in lifelong non-smokers from US data for men and women combined.20 Areas of circles proportional to numbers of controls with usual radon levels in ranges <200, 200-399, 400-599, and 600 Bq/m3
Discussion
United Nations Scientific Committee on the Effects of Atomic Radiation. Sources and Effects of Ionizing Radiation. UNSCEAR 2000 Report to the General Assembly, with Scientific Annexes. Vol I: Sources. New York: United Nations, 2000.
National Research Council. Committee on health risks of exposure to radon (BEIR VI). Health effects of exposure to radon. Washington, DC: National Academy Press, 1999.
International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans. Vol 78. Ionizing radiation. Part 2: Some internally deposited radionuclides. Lyons: IARC, 2001.
Puskin JS. Smoking as a confounder in ecologic correlations of cancer mortality rates with average county radon levels. Health Physics 2003;84: 526-32.
Heid IM, Schaffrath Rosario A, Kreienbrock L, Küchenhoff H, Wichmann HE. The impact of measurement error on studies on lung cancer and residential radon exposure in Germany. J Toxicol Environ Health (in press).
Darby S, Whitley E, Silcocks P, Thakrar B, Green M, Lomas P, et al. Risk of lung cancer associated with residential radon exposure in south-west England: a case-control study. Br J Cancer 1998;78: 394-408.
Darby S, Hill D, Deo H, Auvinen A, Barros-Dios JM, Baysson H, et al. Residential radon and lung cancer: detailed results of a collaborative analysis of individual data on 7,148 subjects with lung cancer and 14, 208 subjects without lung cancer from 13 epidemiological studies in Europe. Scand J Work Environ Health (in press).
Lagarde F, Pershagen G, ?kerblom G, Axelson O, B?verstam U, Damber L, et al. Residential radon and lung cancer in Sweden: risk analysis accounting for random error in the exposure assessment. Health Phys 1997;72: 269-76.
Oberaigner W, Kreienbrock L, Schaffrath Rosario A, Kreuzer M, Wellmann J, Lerrer G, et al. Radon und Lungenkrebs im Bezirk Imst/?sterreich. Fortschritte in der Umweltmedizin. Landsberg am Lech: Ecomed Verlagsgesellschaft, 2002.
Tomáek L, Müller T, Kunz E, Heribanová A, Matzner J, Plaèek V, et al. Study of lung cancer and residential radon in the Czech Republic. Cent Eur J Public Health 2001;9: 150-3.
Auvinen A, M?kel?inen I, Hakama M, Castrén O, Pukkala E, Reisbacka H, et al. Indoor radon exposure and risk of lung cancer: a nested case-control study in Finland. J Natl Cancer Inst 1996;88: 966-72 (plus erratum 1998;90:401-02).
Ruosteenoja E, M?kel?inen I, Ryt?maa T, Hakulinen T, Hakama M. Radon and lung cancer in Finland. Health Phys 1996;71: 185-9.
Baysson H, Tirmarche M, Tymen G, Gouva S, Caillaud D, Artus JC, et al. Case-control study on lung cancer and indoor radon in France. Epidemiology 2004;15: 709-16.
Wichmann HE, Shaffrath Rosario A, Heid IM, Kreuzer M, Heinrich J, Kreienbrock L. Lung cancer risk due to residential radon in a pooled and extended analysis of studies in Germany. Health Physics (in press).
Bochicchio F, Forastiere F, Farchi S, Quarto M, Axelson A. Residential radon exposure, diet and lung cancer: a case-control study in a Mediterranean region. Int J Cancer (in press).
Barros-Dios JM, Barreiro MA, Ruano-Ravina A, Figueiras A. Exposure to residential radon and lung cancer in Spain: a population-based case-control study. Am J Epidemiol 2002;156: 548-55.
Pershagen G, ?kerblom G, Axelson O, Clavensj? B, Damber L, Desai G, et al. Residential radon exposure and lung cancer in Sweden. N Engl J Med 1994;330: 159-64.
Lagarde F, Axelsson G, Damber L, Mellander H, Nyberg F, Pershagen G. Residential radon and lung cancer among never-smokers in Sweden. Epidemiology 2001;12: 396-404.
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((S Darby, professor of medical statistics)